Hepatocellular carcinoma： Therapy and prevention

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and limited therapeutic options. The therapeutic options fall into five main categories: surgical interventions including tumor resection and liver transplantation, percutaneous interventions including ethanol injection and radiofrequency thermal ablation, transarterial interventions including embolization and chemoembolization, radiation therapy and drugs as well as gene and immune therapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for therapeutic recommendations. Though surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, <5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. In order to reduce the morbidity and mortality of HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including drugs, gene and immune therapies as well as primary HCC prevention are of paramount importance. Furthermore, secondary HCC prevention after successful therapeutic interventions needs to be improved in order to make an impact on the survival of patients with HCC. New technologies, including gene expression profiling and proteomic analyses, should allow to further elucidate the molecular events underlying HCC development and to identify novel diagnostic markers as well as therapeutic and preventive targets.     

Hepatocellular carcinoma： Epidemiology, risk factors and pathogenesis

Hepatocellular carcinoma （HCC） is the commonest primary malignant cancer of the liver in the world. Given that the burden of chronic liver disease is expected to rise owing to increasing rates of alcoholism, hepatitis B and C prevalence and obesity-related fatty liver disease, it is expected that the incidence of HCC will also increase in the foreseeable future. This article summarizes the international epidemiology, the risk factors and the pathogenesis of HCC, including the roles of viral hepatitis, toxins, such as alcohol and aflatoxin, and insulin resistance.     

Tuberculous lymphadenitis as a cause of obstructive jaundice： A case report and literature review

Obstructive jaundice secondary to tuberculosis （TB） is extremely rare. It can be caused by TB enlargement of the head of the pancreas, TB lymphadenitis, TB stricture of the biliary tree, or a TB mass of the retroperitoneum. A 29-year-old man with no previous history of TB presented with abdominal pain, obstructive jaundice, malaise and weight loss. Ultrasonography （US）, computer tomography （CT） scan and endoscopic retrograde cholangiopancreatography （ERCP） were suggestive of a stenosis of the distal common bile duct （CBD） caused by a mass in the posterior head of the pancreas. Tumor markers, CEA and CA19-9 were within normal limits. At operation, an enlarged, centrally caseous lymph node of the posterior head of the pancreas was found, causing inflammatory stenosis and a fistula with the distal CBD. The lymph node was removed and the bile duct resected and anastomosed with the Roux-en Y jejunal limb. Histology and PCR based-assay confirmed tuberculous lymphadenitis. After an uneventful postoperative recovery, the patient was treated with anti-tuberculous medication and remained well 2.5 years later. Though obstructive jaundice secondary to tuberculous lymphadenitis is rare, abdominal TB should be considered as a differential diagnosis in immunocompromised patients and in TB endemic areas. Any stenosis or fistulation into the CBD should also be taken into consideration, and biliary bypass surgery be performed to both relieve jaundice and prevent further stricture.     

Hepatocellular carcinoma in Lebanon： Etiology and prognostic factors associated with short-term survival

AIM: To study the epidemiology of HCC in Lebanon and prognostic factors predictive of early mortality. METHODS: An observational follow-up cohort study of HCC cases diagnosed over a five-year period was carried out. Multivariate analysis was conducted to identify prognostic factors in comparison to Cancer of the Liver Italian Program (CLIP) score. Multiple variables including the etiology of underlying liver disease, the demographic characteristics of patients, and the severity of liver disease evaluated by the Child-Pugh score were studied. Tumor parameters included the time of diagnosis of HCC, alpha-fetoprotein level, number and size of nodules, presence of portal vein thrombosis, and treatment modalities. Death or loss of follow-up was considered as an end-point event. RESULTS: Ninety-two patients (mean 60.5 +/- 22.3 years) were included. Etiology of underlying disease was hepatitis B, C, and alcohol in 67%, 20%, and 23.5% respectively. Child-Pugh class at diagnosis was A, B, and C in 34.8%, 39.3% and 25.8% respectively. Overall survival was 44.8%, 32.8% and 17.6% at 1, 2 and 3 years respectively (mean F/U 40.2 +/- 23.5 mo). Multivariate analysis identified three predictors of early mortality (< 6 mo): bilirubin > 3.2 mg/dL (P < 0.01), HCC as first presentation of liver disease (P = 0.035), and creatinine > 1 mg/dL (P = 0.017). A score based on these variables outperformed the CLIP score by Cox proportional hazard. ROC curve showed both models to be equivalent and moderately accurate. CONCLUSION: HBV is the leading cause of HCC in Lebanon. Independent predictors of early mortality are elevated bilirubin, creatinine and HCC as first manifestation of disease. Prospective validation of a score based on these clinical parameters in predicting short-term survival is needed.     

Hepatocellular carcinoma treated with interventional procedures： CT and MRI follow-up

In the past decade,a variety of interventional procedureshave been employed for local control of hepatocellularcarcinoma(HCC).These include transcather arterialchemoembolization(TACE)and several tumour ablationtechniques,such as percutaneous ethanol injection(PEI),radio-frequency ablation(RFA),or percutaneous microwavecoagulation therapy(PMC),laser-induced interstitialthermotherapy(LITT),etc.For a definite assessment ofthe therapeutic efficacy of interventional procedures,histological examination using percutaneous needle biopsymay be the most definite assessment of the therapeuticefficacy of interventional therapy,however,it is invasiveand the specimen retrieved does not always represent theentire lesion owing to sampling errors.Therefore,computedtornography(CT)and magnetic resonance imaging(MRI)playa crucial role in follow-up of HCC treated by interventionalprocedures,by which the local treatment efficacy,recurrentdisease and some of therapy-induced complications areevaluated.Contrast enhanced axial imaging(CT or MRimaging)may be the most sensitive test for assessing thetherapeutic efficacy.The goal of the review was to describethe value of CT and MRI in the evaluation of interventionaltreatments.     

经肝动脉化疗栓塞治疗肝细胞癌：使用不同栓塞剂患者生存期的对比

目的：HCC的经动脉化疗栓塞（TACE）最理想的栓塞剂还没有被确定。这项研究报导了使用明胶海绵粉末和聚乙烯醇（PVA）行TACE术治疗肝细胞癌的结果。[第一段]     

Hepatocellular carcinoma： Defining the place of surgery in an era of organ shortage

Liver resection （LR） and transplantation offer the only potential chance of cure for patients with hepatocellular carcinoma （HCC）. Historically, all patients were treated by hepatic resection. With the advent of liver transplantation （LT） patients with HCC were preferentially placed on the waiting list for LT. However, early experience with LT was associated with a high rate of tumour recurrence and poor long-term survival. The increasing scarcity of donor livers resulted in restrictions being placed on tumour size, and an improvement in patient survival. To date there have been no randomised clinical trials comparing LR to LT. We review the evidence supporting LR and/or LT for HCC and discuss the role of neoadjuvant therapy. The decision of whether to resect or transplant remains debatable and is often determined by centre experience, availability of LT and donor organs.     

介入治疗恶性梗阻性黄疸的临床疗效评价

恶性梗阻性黄疸内、外科治疗均效果欠佳,目前通常采用经手术或介入方法进行各种内外引流[1].介入方法以其操作简便、创伤小、并发症少及成功率高等优势已经成为临床治疗恶性梗阻性黄疸的常用方法.作为一种姑息疗法, 其对恶性原发病并无治疗作用,且如果不能控制原发肿瘤的发展,支架短期内会被肿瘤填塞,使支架失去功能.如何提高疗效,延长患者生存时间,防止上述情况的发生成为现实问题.本研究将经皮经胆道引流术(PTCD)和辅以动脉插管化疗灌注或栓塞术(TAI/TAE)相结合,并与单纯行PTCD治疗进行对比分析,寻找治疗恶性梗阻性黄疸的新方法,以提高介入治疗的疗效.     

Hepatocellular carcinoma presenting with obstructive jaundice: a clinicopathological study of eight cases

BACKGROUND/AIMS: The prognosis of icteric type hepatocellular carcinoma is extremely poor, not only because of obstructive jaundice, but also because of difficulties for early diagnosis. The aim of this study is to evaluate characteristics of icteric hepatocellular carcinoma for early diagnosis. METHODOLOGY: Eight patients with icteric hepatocellular carcinoma among 326 patients with hepatocellular carcinoma in our hospitals were retrospectively examined by laboratory data, image studies and pathology studies. RESULTS: Most cases were already advanced, with a portal tumor thrombus at the time of diagnosis. Imaging studies fail to reveal tumors because this type of hepatocellular carcinoma has an irregular faint margin and has lost the characteristic pattern of hepatocellular carcinoma, such as capsular formation or early enhancement. Pathology observations demonstrated poorly or moderately differentiated hepatocellular carcinoma in all our cases. CONCLUSIONS: This type of hepatocellular carcinoma should be considered in cirrhotic patients with obstructive jaundice or in patients with high tumor marker levels even if image studies fail to reveal tumors. For better prognosis, combination therapies such as biliary drainage, support for portal flow as well as treatment for the hepatocellular carcinoma, are necessary.     

Hepatocellular carcinoma: diagnosis and treatment

Hepatocellular carcinoma is the most frequent primary malignancy of the liver and appears to be rising in incidence in the United States and other developed western countries. Imaging studies play a key role in diagnosis of hepatocellular carcinoma, and more and more commonly, patients are being diagnosed at an asymptomatic stage. The use of triphasic computed tomography scanning and improved magnetic resonance imaging equipment and protocols has led to greater sensitivity and specificity for these techniques in diagnosis of hepatocellular carcinoma. Accurate staging of hepatocellular carcinoma is important in determining prognosis and in helping decide the best treatment for each patient. No one staging system appears optimal, but important factors to be considered are the size of the tumor, severity of underlying liver disease, and the functional status of the patient. Liver transplantation has grown in importance as a treatment for hepatocellular carcinoma but may be limited by availability of donor organs and long waiting times. This situation may be improved by greater use of living donor liver transplantation. Hepatic resection remains an important treatment modality for hepatocellular carcinoma, particularly in the absence of cirrhosis. Tumor ablation by alcohol injection or radiofrequency ablation is associated with favorable outcomes and may be considered a potentially curative treatment. Early diagnosis of hepatocellular carcinoma remains a key goal in improving the poor prognosis of this form of liver cancer. Identifying hepatocellular carcinoma at an early stage is often associated with having better treatment options for patients with small, asymptomatic tumors.     

Hepatocellular carcinoma with obstructive jaundice successfully treated with a self-expandable metallic stent

We report on a 71-year old man with hepatocellular carcinoma (HCC) whose obstructive jaundice was successfully treated with external irradiation and a self-expandable metallic stent (EMS); Wallstent; Schneider (Europe) AG, Bülach, Switzerland. He was admitted to our hospital because of jaundice. HCC was found in S8; the tumor had invaded the bile duct with growth in the common hepatic duct. Endoscopic nasobiliary drainage was performed with difficulty. Radiation therapy to the stenosis enabled us to place a Wallstent endoscopically. He survived without icterus for 1 year. (Received Oct. 31, 1997; accepted May 22, 1998)     

Hepatocellular carcinoma in patients with renal dysfunction: Pathophysiology,prognosis, and treatment challenges

The population of patients with hepatocellular carcinoma (HCC) overlaps to a high degree with those for chronic kidney disease (CKD) and end-stage renal disease (ESRD). The degrees of renal dysfunction vary, from the various stages of CKD to dialysis-dependent ESRD, which often affects the prognosis and treatment choice of patients with HCC. In addition, renal dysfunction makes treatment more difficult and may negatively affect treatment outcomes. This study summarized the possible causes of the high comorbidity of HCC and renal dysfunction. The possible mechanisms of CKD causing HCC involve uremia itself, long-term dialysis status, immunosuppressive agents for postrenal transplant status, and miscellaneous factors such as hormone alterations and dysbiosis. The possible mechanisms of HCC affecting renal function include direct tumor invasion and hepatorenal syndrome. Finally, we categorized the risk factors that could lead to both HCC and CKD into four categories: Environmental toxins, viral hepatitis, metabolic syndrome, and vasoactive factors. Both CKD and ESRD have been reported to negatively affect HCC prognosis, but more research is warranted to confirm this. Furthermore, ESRD status itself ought not to prevent patients receiving aggressive treatments. This study then adopted the well-known Barcelona Clinic Liver Cancer guidelines as a framework to discuss the indicators for each stage of HCC treatment, treatment-related adverse renal effects, and concerns that are specific to patients with pre-existing renal dysfunction when undergoing aggressive treatments against CKD and ESRD. Such aggressive treatments include liver resection, simultaneous liver kidney transplantation, radiofrequency ablation, and transarterial chemoembolization. Finally, focusing on patients unable to receive active treatment, this study compiled information on the latest systemic pharmacological therapies, including targeted and immunotherapeutic drugs. Based on available clinical studies and Food and Drug Administration labels, this study details the drug indications, side effects, and dose adjustments for patients with renal dysfunction. It also provides a comprehensive review of information on HCC patients with renal dysfunction from disease onset to treatment.     

Hepatocellular carcinoma: From diagnosis to treatment

Hepatocellular carcinoma(HCC) is the sixth most prevalent malignancy worldwide and is a rising cause of cancer related mortality. Risk factors for HCC are well documented and effective surveillance and early diagnosis allow for curative therapies. The majority of HCC appears to be caused by cirrhosis from chronic hepatitis B and hepatitis C virus. Preventive strategies include vaccination programs and anti-viral treatments.Surveillance with ultrasonography detects early stage disease and improves survival rates. Many treatment options exist for individuals with HCC and are determined by stage of presentation. Liver transplantation is offered to patients who are within the Milan criteria and are not candidates for hepatic resection. In patients with advanced stage disease, sorafenib shows some survival benefit.     

Hepatocellular carcinoma in developing countries: Prevention, diagnosis and treatment

Hepatocellular carcinoma(HCC)occurs commonly and with increasing frequency in developing countries,where it also carries an especially grave prognosis.The major risk factor for HCC in these regions is chronic hepatitis B virus(HBV)infection,although dietary exposure to aflatoxin B1 also plays an important etio-logical role.Prevention of HCC in developing regions is unlikely in the foreseeable future.Although an effec-tive vaccine against HBV is available,the percentage of babies born in developing countries that receive the full course of immunization remains low.Moreover,the usually long interval between infection with HBV and the development of HCC means that 30 to 50 years will elapse before the full effect of the vaccine will be realized.Practical measures to prevent aflatoxin B1 ex-posure are not in place.Serumα-fetoprotein levels are a useful pointer to the diagnosis of HCC in low-income countries,but definitive diagnosis is hampered both by the lack of the sophisticated imaging equipment now available in developed countries and by obstacles to obtaining histological proof.In the majority of patients in low-income regions,the tumor is inoperable by the time the patient presents.Hepatic resection is seldom possible in sub-Saharan Africa,although the tumor is successfully resected in a larger number of patients in China.Liver transplantation for HCC is rarely performed in either region.Sophisticated new radiotherapy tech-niques are not available in developing countries.The beneficial effects of the multikinase inhibitor,sorafenib,are encouraging,although financial considerations may restrict its use in low-income countries.     

Imaging diagnosis of obstructive jaundice

In the past, before the development of biochemical tests for serum enzymes, differentiation between obstructive (surgical) and parenchymal (medical) jaundice was difficult. It was based mainly on patient history, physical examination and the experience of the physician, and the definitive diagnosis depended on surgical exploration. Even with known serum aminotransferase and alkaline phosphatase levels, a distinction between the two types of jaundice was not always certain. Then came the era of new imaging techniques. With the development of direct cholangiography followed by x-ray CT and real-time ultrasonography (US), differential diagnosis of surgical and medical jaundice is no longer a problem. In the clinical setting, the current issue is how quickly and how less invasively the diagnosis could be made. In this chapter, current imaging diagnosis in patients with obstructive jaundice will be discussed, along with its differentiation from medical jaundice.     

Hepatocellular apoptosis after hepatectomy in obstructive jaundice in rats

AIM: To investigate the hepatocellular apoptosis after hepatectomy in obstructive jaundice and biliary decompression rats. METHODS: After bile duct ligation for 7 days, rats were randomly divided into OB group in which the rats underwent 70% hepatectomy, OB-CD group in which the rats underwent hepatectomy accompanied by choledochoduodenostomy, CD-Hx group in which the rats underwent choledochoduodenostomy and then received 70% hepatectomy on the fifth day after biliary decompression. The control group (Hx group) only underwent hepatectomy. RESULTS: The level of total serum bilirubin and serum enzymes was significantly lower in CD-Hx group than in OB-CD and OB groups on day 1, 3 and 5 after hepatectomy. The apoptotic index was significantly lower in CD-Hx group than in OB-CD and OB groups on day 3 and 5. The oligonucleosomal DNA fragments and Caspase-3 activity were also lower in CD-Hx group than in OB-CD and OB groups 3 days after hepatectomy, without differences between CD-Hx and Hx groups. CONCLUSION: Hepatocellular apoptosis plays vital roles in jaundice rats, and biliary decompression is more effective in treatment of patients with severe jaundice before operation.